OHSU study to formulate a computational model of ovarian development

Karen Watanabe

09/11/13 Portland, Ore.

Using computational models that mimic biological processes to reduce animal toxicity experiments is the hope of Oregon Health & Science University scientist Karen Watanabe, Ph.D..

“A goal of my research is to develop predictive computational models that can be used to screen chemicals and predict potential toxicity thereby reducing the number of laboratory animals used in toxicity testing,” Watanabe says.

A recent grant from the Alternatives Research & Development Foundation will help move that goal forward by funding a new study to formulate a computational model of mammalian ovarian development to reduce animal testing of putative reproductive toxicants.

Dr. Watanabe, a professor in the Division of Environmental & Biomolecular Systems at  OHSU’s Institute of Environmental Health, says she will utilize input data from in vitro studies that characterize chemical effects at the molecular and cellular levels to predict effects on ovarian development.

The first step in the project is to compile published data to formulate a model with biologically based parameters that can utilize results from in vitro tests being developed under the paradigm of the U.S. National Academy of Sciences report Toxicity Testing for the 21st Century. The landmark report released in 2007 envisioned using computational systems biology models as one way to increase the efficiency in toxicity testing and decreased animal usage.

The research team will formulate a conceptual model of the regulatory network involved in normal ovarian development. Then will formulate a mathematical model that simulates the growth of the different cell populations (i.e., germ cells and somatic cells including granulosa cells, theca cells, and stromal cells) in the context of a developing ovary.

Outcomes of this research will include a computational model and a graphical representation of the biochemical regulatory network during ovarian development. The conceptual model will likely include a greater level of biological detail, than the computational model that requires quantitative measurements of biological changes over time. Watanabe plans to implement a simplified version of the conceptual model and then revise it as additional data become available.

Dr. Watanabe has devoted her research career to developing computational models for a variety of biological systems including; physiologically based toxicokinetic models of benzene for rats, mice, and humans; bioaccumulation of polycyclic aromatic compounds in crayfish and aquatic food webs; and most recently the hypothalamic-pituitary-gonadal axis in male and female fathead minnows and oocyte growth dynamics in fathead minnows.

“We expect to have a computational model that will simulate molecular and cellular processes, and predict experimentally observed numbers of cells within a developing ovary from conception to the formation of primordial follicles,” Watanabe says.


OHSU Institute of Environmental Health believes preventative medicine starts with a healthy environment. There is overwhelming evidence that human activities and the global climate are affecting environmental health and sustainability. Increasingly, these consequences are causing serious implications for human health. IEH seeks to develop scientific understanding in environmental and biomolecular systems that  elucidates environmental processes and their links to human health.